UBC Theses and Dissertations
Skin mechanics, intradermal delivery and biosensing with hollow metallic microneedles Ranamukhaarachchi, Sahan
Microneedles (MNs) have gained significant attention over the past decade in drug delivery and biosensing due to their minimally-invasive and less painful nature of use compared to intramuscular/subcutaneous injections, and significant biological benefits. Several fundamental processes enabling MN functionality have not been completely understood, including mechanical interaction between MNs and skin for targeted depth penetration; and precise quantification of fluid delivery in the skin. This thesis presents novel materials, and methodologies for evaluating MN interactions with skin, and investigates the performance of hollow MNs in both intradermal fluid drug delivery and biosensing. A micromechanical comparison between human skin and porcine skin was performed using to determine their mechanical behavior affecting MN insertions. Stratum corneum (SC) of human skin was significantly stiffer (117 ± 42 MPa) than porcine skin (81 ± 32 MPa), requiring higher force of MN insertion to rupture the SC in human skin (107 ± 17 mN) than porcine skin (96 ± 23 mN). An artificial mechanical skin model was developed layer-by-layer to simulate tough human skin (MN insertion force 162 ± 11 mN) and to study the dynamics of MN insertion. Key factors that affected MN insertions into skin, including velocity of impact and total energy delivered to the skin, were identified. ID fluid delivery by hollow MNs was assessed using a novel method involving the low-activity radiotracer technetium-99m pertechnetate (⁹⁹mTcO₄₋). Its delivery allowed accurate quantification of fluid delivered into the skin, back-flowed to the skin surface, and total fluid ejected from the syringes via ID devices with sub-nanoliter resolution. Hollow MNs performed more accurate ID injections than conventional needles (93% vs. 69-87% of fluid per 0.1 mL injection volume). A MN-optofluidic biosensing platform capable of eliminating blood sampling was developed with MNs that can access dermal interstitial fluid that contains numerous drugs at concentrations comparable to blood. The MN lumen was functionalized to collect, trap and detect drugs in 0.6 nL of sample. The optofluidic components provided specific high-sensitivity absorbance measurements for drug binding using enzyme-linked assays. Streptavidin-horseradish peroxidase (LoD = 60.2 nM) and vancomycin (LoD = 84 nM) binding validated this point of care system.
Item Citations and Data
Attribution-NonCommercial-NoDerivatives 4.0 International